Project Summary Tobacco smoking is one of the most preventable causes of morbidity and mortality worldwide and has become a growing epidemic in developing countries in Africa. Among HIV+ individuals on antiretroviral therapy, smoking causes more life-year loss than HIV infection. While both behavioral approaches and pharmacotherapy are typically used together in high income countries, pharmacotherapy is largely unavailable in sub-Saharan Africa due to cost. Instead, developing and evaluating behavioral smoking cessation interventions, which could be realistically disseminated is a priority for addressing tobacco use among persons with HIV in countries such as Botswana. Yet, unique aspects of HIV (e.g., high rate of depressive symptoms) and delivery of care in such settings (e.g., decentralized, limited infrastructure) must be considered when designing a behavioral approach in LMICs such as Botswana. Depressive symptoms are common in HIV populations and often comorbid with smoking, and addressing depressive symptoms has been related to better smoking cessation rates. Behavioral activation therapy, rooted in a behavioral economics framework, has been effective at treating depression and preliminary data in the US, including in our group, suggests that it may effectively address smoking as well. Behavioral activation aims to increase engagement in healthy rewarding activities (i.e., substitute reinforcers) by reducing patterns of avoidance, withdrawal, and inactivity, and decrease activities that enhance the rewarding aspects of smoking (i.e., complementary reinforcers). In a parallel way, problem solving approaches have been used with HIV populations for behavior change regarding medication adherence, have also been successful at decreasing depressive symptoms, and are ideally suited for helping smokers select and implement personalized behavioral activation activities to quit smoking. We therefore created the novel Behavioral Activation/Problem Solving for Smoking Cessation (BAPS-SC), culturally adapted it and pilot tested it in Botswana and found it to be feasible and appealing and to have preliminary evidence of efficacy. We will conduct a 1:1 randomized trial comparing a BAPS-SC with standard counseling for smoking cessation in 650 HIV+ smokers in Botswana. We will leverage HIV care sites and deliver the interventions by phone to extend the reach of skilled practitioners. We will also assess whether depressive symptoms moderate the effect of BAPS-SC and test our proposed mediating pathways for the interventions' effects This project will determine whether the novel intervention is superior to standard counseling to establish a new paradigm for LMIC smoking cessation programs. We will also further our understanding of whether depressive symptoms, reinforcers, and problem solving are modifiable mediators of smoking. Leveraging the HIV care infrastructure will facilitate scale-up in sub-Saharan African settings where HIV is common and smoking continues to emerge as a threat to HIV+ individuals' health and survival.